6: Anticoagulants, Thrombolytics, Antiplatelet agents & Antifinrinolytics

Question 0

What rae Thrombolytics/Fibrinolytic’s?

Answer 0

Substances that promote the destruction of already formed blood clots or thrombi (i.e lyse thrombi) by disrupting the fibrin mesh

Question 1

What are Anticoagulants?

Answer 1

Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of thrombi.

Question 2

What are Anti platelets?

Answer 2

Drugs that reduce the adhesion and aggregation of platelets

Question 3

What are Antifibrinolytics?

Answer 3

Drugs that promote the formation of clots and prevent excessive bleeding

Question 4

What do Anticoagulants inhibit?

Answer 4

The action or formation of one or more of the clotting factors

Question 5

Why should Anticoagulants be treated with caution?

Answer 5

They create an immediate defect (minutes when given IV, hours when given orally) in the clotting mechanism and should be treated with caution.

Question 6

What is the range between sufficient therapy and hemorrhagic risk?

Answer 6

The risk is narrow and varies considerably from patient to patient.

• A large # of unrelated drugs also affect the dose of the anticoagulant needed to produce a desired effect.
• Individual treatment & frequency lab tests are imperative.

Question 7

What are the Anticoagulants be divided into?

Answer 7

1) Indirect Thrombin Inhibitors (basically HEPARIN :)
2) Coumarin Anticoagulants (basically WARFARIN)
3) Direct THROMBIN INHIBITORS
4) DIRECT FACTOR X INHIBITORS

Question 8

What is Heparin ?

Answer 8

Commercial heparin is actually a mixture of heparins (protein molecules) w/ a wide range of molecular weights

Question 9

What are the 2 MOST common preparations:

Answer 9

1) Unfractionated heparin (UFH)–Heparin Sodium

2) Low-molecular-wt heparin (LMWH)– Fragmin, Innohep, Lovenox

Question 10

How does Heparin work ?

Answer 10

Heparin stimulates Antithrombin III (this neutralizes the activity of factor & other factors)

Question 11

What occurs to the intrinsic system without factor Xa?

Answer 11

Prothrombin can’t be converted into thrombin, which ultimately prevents FIBRIN formation from FIBRINOGEN

Question 12

Why is Heparin called an “indirect thrombin inhibitor” ?

Answer 12

Stimulates heparin cofactor II which inhibits thrombin

Question 13

What is Unfractionated Heparin (UFH)

Answer 13

**Effective parenteral ANTICOAGULANT for the PREVENTION of clots!

-Discovered in 1916 and has been used for more than 50 years

Question 14

Why is Unfractionated Heparin (UFH) not effective if given orally?

Answer 14

Not absorbed if given orally as heparin proteins are destroyed by stomach acidity.

***Given by IV (bolus or infusion)

Question 15

When UFH binds to a number of plasma proteins (or endothelial cells & macrophages) what happens?

Answer 15

It reduces its anticoagulation activity & causes a rather larger variability of anticoagulant response among patients.

***The relationship between UFH dose & UFH response is a bit tricky

Question 16

Since the anti-coagulant response to UFH varies among patients what is it important to do?

Answer 16

It is standard practice to adjust the dose of UFH & monitor its clinical effectiveness w/ the activated partial thromboplastin time (APTT)

Question 17

What is the normal APTT time?

Answer 17

25-36 seconds

**Therapeutic levels of UFH will typically prolong the aPTT (activated partial thromboplastin time) to 2-2.5 times that of the normal value

Question 18

How can LMWH preparations be used?

Answer 18

In-hospital or out-of-hospital setting b/c they can be administered SC(typically w/ pre-filled needle/syringe systems) on a body weight basis w/out the needle for lab monitoring

Question 19

What is the only major coumarin anticoagulant in the US?

Answer 19

Warfarin (Coumadin)

**Can lead to death by hemorrhage or internal bleeding

Question 20

How does Warfarin work?

Answer 20

Inhibits blood clotting mechanisms by interfering w/ the hepatic synthesis of the VITAMIN K DEPENDENT CLOTTING FACTORS (2, 7, 9, 10)

Question 21

What is the long-term treatment or prophylaxis of Warfarin?

Answer 21

1) Venous thrombosis
2) PE

*Post-MI and post-op (after cardiac, vascular surgery) patients. Prevention of systemic thromboembolism in patients w/ prosthetic heat valves or atrial fibrillation

Question 22

What is INR?

Answer 22

The therapeutic range for oral anticoagulation therapy is defined in terms of the international normalized ration (INR)

*****Therapeutic levels of warfarin should be adjusted to achieve an INR of 2.0-3.0

Question 23

What are the Key Drug-Drug Interactions Warfarin that inhibit warfarin metabolism(inhibit breakdown) ?

Answer 23

These inhibit warfarin metabolism:

1) Cimetidine (Tagamet) –acid reflux
2) Acetaminophen (Tylenol)
3) High dose, acute alcohol

***Keeps it around in the blood longer :)

Question 24

What are the Key Drug-Drug Antibiotic Interactions that inhibit warfarin metabolism (inhibiting its breakdown)?

Answer 24

1) Azithromycin (Zithromax) 2) Ciprofloxacin 3) Clarithromycin 4) Erythromycin ***INR goes up!! (when inhibited) and can lead to bleeding. (Sticks around a lot long and accumulated in the body)

Question 25

How can synthetic thyroid hormones affect the catabolism of many clotting factors & can potentiate the effects of warfarin?

Answer 25

INCREASE ( inhibit the anticoagulant action-blood clots)

Question 26

Which Drugs stimulate WARFARIN metabolism (breaking it down fast) and may diminish the desired effects?

Answer 26

1) Chronic alcohol use 2) Phenytonin (Dilantin) --seizure meds ***Oral contraceptives INCREASE the synthesis of many factors and can reduce the effects of warfarin (causes blood clots) Note: Rhis DECREASES the INR !!

Question 27

What does interactions involving warfarin & food rich in vitamin K result in?

Answer 27

DECREASED warfarin effects by stimulating the synthesis of vitamin K dependent clotting factors. ***Often b/c of leafy vegetables (maintain consistent daily intake)

Question 28

What are Warfarin overdoses typically treated by?

Answer 28

With vitamin K & transfusion

Question 29

What are the side effects of Warfarin?

Answer 29

Bleeding is most common side effect. Occurs most often from the mucous membranes of the GI tract & the genitourinary tract.

Question 30

Why is Warfarin contraindicated during pregnancy (Category X) ?

Answer 30

Should not be used during pregnancy b/c it crosses the placenta & is teratogenic. ***Breast feeding should also be avoided during warfarin therapy!!

Question 31

What are the Direct Thrombin Inhibitors?

Answer 31

Example: Dabigatran (Pradaxa) 1st orally direct thrombin inhibitor!!! If offers an alternative to warfarin as an orally administered anticoagulant. **This NEW drug does not require frequent blood tests for INR, doesn't affect vitamin K or antibiotic levels :) :)

Question 32

What is an example of a DIRECT FACTOR X INHIBITORS?

Answer 32

Xarelto | newly release in 2011

Question 33

What are Thrombolytics/Fibrinolytics?

Answer 33

Rapidly lyse thrombi when administered intravenously by catalyzing the formation of plasmin from plasminogen **Bust clot to regulate regular blood flow

Question 34

What are examples of Thrombolytics/Fibrinolytics?

Answer 34

1) Streptokinase 2) Urokinase 3) Synthetic tPA 4) Others

Question 35

Why would you administer Thrombolytics/Fibrinolytics?

Answer 35

For acute Mi, acute ischemic stroke and PE. ***for best results, Thrombolytics work best the sooner they are initiated from the onset of the event.

Question 36

What are the main classes of Antiplatelet agents?

Answer 36

1) Cyclooxygenase Inhibitors( aspirin) 2) Thienopyridines (ADP Inhibitors) 3) GP IIb/IIIa inhibitors

Question 37

How does Aspirin act on platelets?

Answer 37

By inhibiting the synthesis of TXA2 one of the substances that helps make the platelets sticky & more likely to aggregate

Question 38

What are the Thienopyridines (ADP Inhibitors?)

Answer 38

Prevent the binding of ADP to its receptor on platelets, thereby inhibiting an important pathway that leads to platelet aggregation.

Question 39

What is the main drug that fits in this category ( Thienopyridines (ADP Inhibitors?)

Answer 39

CLOPIDOGREL (PLAVIX) or new one Effient (ADP inhibitor)

Question 40

What are GP IIb/IIIa inhibitors?

Answer 40

These inhibit the activation of glycoproteins IIb/IIIa receptors on platelets, inhibiting the "final common pathway" for platelet aggregation

Question 41

What is an example of a drug that is an GP IIb/IIIa inhibitors?

Answer 41

ABCIXIMAB (REOPRO) **Administered IV w/ an initial bolus followed by constant infusion

Question 42

What are Antifibrinolytics? What is an example?

Answer 42

Inhibits the activation of plasminogen to plasmin (***Counteracts the Tissue plasminogen activator tPA) Example= Tranexamic acid (reduce clots from being dissolved, keep them around longer)

Question 43

What is Tranexamic acid used for in dentistry?

Answer 43

Used in the form of a 5% mouth rinse after extractions or surgery in patients w/ prolonged bleeding time, e.g from acquired or inherited disorders ****PROMOTES CLOTS